[Amentoflavone inhibits M1 polarization of THP-1-derived foam cells by activating PPAR-α/γ]

Area of Science:

• Immunology and Cell Biology
• Pharmacology and Natural Products

Background:

• Macrophage polarization, particularly to the M1 phenotype, plays a critical role in inflammatory diseases.
• THP-1 cells are a widely used human monocytic cell line for studying macrophage differentiation and function.
• Foam cell formation is a key process in atherosclerosis, driven by lipid accumulation and inflammation.

Purpose of the Study:

• To elucidate the mechanism by which amentoflavone inhibits the M1 polarization of THP-1-derived foam cells.
• To investigate the molecular targets and downstream effects of amentoflavone on macrophage phenotype.
• To assess the potential of amentoflavone as an anti-inflammatory agent in the context of foam cell biology.

Main Methods:

• THP-1 cells were differentiated into M1 macrophages using PMA, LPS, and rhlFN-γ.
• M1 polarization was confirmed via morphological assessment and RT-qPCR for IL-6 and TNF-α.
• Amentoflavone treatment effects on cytokine and gene expression (IL-6, IL-10, TNF-α, TGF-β, PPAR-α/γ, Arg-1, Fizz1) were analyzed using ELISA, RT-qPCR, and Western blotting.
• Molecular docking simulations were performed to predict binding interactions between amentoflavone and PPAR-α/γ.

Main Results:

• Amentoflavone effectively prevented the induced M1 polarization of THP-1 cells.
• Amentoflavone significantly down-regulated mRNA expression of IL-6 and TNF-α.
• Amentoflavone up-regulated mRNA expression of IL-8 and TGF-β, and increased protein expression of PPAR-α/γ, Arg-1, and Fizz1.
• Molecular docking indicated amentoflavone binds to the surface of PPAR-α/γ.

Conclusions:

• Amentoflavone inhibits M1 macrophage polarization through the activation of PPAR-α/γ.
• This activation restores the expression of beneficial genes such as Arg-1 and Fizz1.
• Amentoflavone demonstrates potential as a therapeutic agent for modulating macrophage phenotype and mitigating inflammation.